TEL AVIV, Israel — The Israeli military shot down an Iranian drone launched from Syria into Israeli airspace early Saturday in what the military described as a "severe and irregular violation of Israeli sovereignty."

The military said its planes faced "massive" anti-aircraft fire from Syria which forced two Israeli pilots to abandon their F-16 jet as they sought to target the drone's launching pad. One pilot was severely injured and both were taken to hospital for medical treatment after they landed in Israeli territory.

In response, Israel launched a "large-scale attack" on at least a dozen Iranian targets in Syria, marking a escalation in tensions along the country's northern border.

"Israel holds Iran and its Syrian hosts responsible for today’s aggression," Israel Prime Minister Benjamin Netanyahu said Saturday, noting that he had warned of Iranian aggression for some time. "We will continue to do whatever is necessary to protect our sovereignty and our security."

The Israeli strikes marked its most significant engagement since the fighting in neighboring Syria began in 2011 and said Iran would be held responsible for its outcome.

"This is a serious Iranian attack on Israeli territory. Iran is dragging the region into an adventure in which it doesn't know how it will end," Israel's chief military spokesman, Brig. Gen. Ronen Manelis, said in a special statement. "Whoever is responsible for this incident is the one who will pay the price."

Israel has mostly stayed out of the prolonged fighting in Syria, wary of being drawn into a war in which nearly all the parties are hostile toward it. It has recently been warning of the increased Iranian presence along its border, but military spokesman Lt. Col. Jonathan Conricus said Saturday's incident marked the most "blatant and severe violation of Israeli sovereignty" yet.

He said Israel has no interest in further escalation but that it would "extract a heavy price" for such aggression.

He said Iran was "playing with fire" by infiltrating Israeli airspace, and stressed that the unmanned aircraft Israel shot down was "on a military mission sent and operated by Iranian military forces."

He said Israel recovered the dispatched drone, which was clearly Iranian.

In response, Conricus said Israeli jets destroyed the Iranian site in central Syria that launched it. Upon their return, the jets came under heavy Syrian anti-aircraft fire. The pilots of one of the F-16s had to escape and the plane crashed. It's unclear whether the plane was actually struck or if the pilots abandoned their mission for a different reason.

If the plane was in fact shot down by enemy fire, it could mark the first such instance for Israel since 1982 during the first Lebanon war.

Israel's President Reuven Rivlin praised the nation's security forces and spoke to the injured pilot.

"My heart is with you and your comrades, and I hope that I will meet you soon," Rivlin said. "You and the entire squadron have proven that you do not come back until your mission is fulfilled, and I thank God together with the entire nation that you have returned."

In subsequent attacks, Israel struck four additional Iranian positions and eight Syrian sites in Syria. The military said significant damage was caused.

Major Adrian Rankine-Galloway, a Pentagon spokesman, said on Saturday that the Department of Defense did not participate in Israel's military operation, but said they fully supported the U.S.'s "closest security partner in the region," especially in its "inherent right to defend itself against threats to its territory and its people."

"We share the concerns of many throughout the region that Iran's destabilizing activities that threaten international peace and security," Rankine-Galloway said, "and we seek greater international resolve in countering Iran's malign activities."

The U.S. State Department said Saturday that "The United States is deeply concerned about today's escalation of violence over Israel's border and strongly supports Israel's sovereign right to defend itself."

The United States is deeply concerned about today's escalation of violence over Israel's border and strongly supports Israel's sovereign right to defend itself. https://t.co/iTnwLaHcmx

Gen. Hossein Salami, acting commander of Iran's Revolutionary Guard, did not acknowledge Israel's claim it shot down the drone. "We do not confirm any such news from Israel," he said.

Syria's Defense Ministry said in statements on its website that its air defenses responded successfully to the Israeli operation and hit more than one plane. "The Israeli enemy has once again attacked some of our military bases in the southern area and our air defenses responded and foiled the aggression," it said.

Russia's foreign ministry expressed concern later Saturday over the Israeli missile strikes in Syria and urged the sides to avoid escalating the situation.

In a statement, the ministry said "of particular concern is the danger of escalation of tension within and around de-escalation zones in Syria, the creation of which has become an important factor in reducing violence on Syrian soil."

Lebanese militant group Hezbollah hailed Syria's response to Israel's attack on Iranian and Syrian bases in Syria, saying it signals "a new strategic phase" that puts an end to violation of Syrian territories.

Netanyahu and Defense Minister Avigdor Lieberman convened the top brass at military headquarters in Tel Aviv to discuss further response.

Israel has long complained about the involvement of archenemy Iran, and Hezbollah, in the Syrian war. The Shiite allies have sent forces to back Syrian President Bashar Assad, who appears headed toward victory after years of fighting. Israel has said it will not accept a permanent military presence by Iran and its Shiite allies in Syria, especially near the Israeli border.

Israel has been warning of late of the increased Iranian involvement along its border. It fears Iran could use Syrian territory to stage attacks or create a land corridor from Iran to Lebanon that could allow it to transfer weapons more easily to Hezbollah.

Israel has shot down several drones that previously tried to infiltrate its territory from Syria. The targeting of an Iranian site in response, however, marks an escalation in the Israeli retaliation.

"The Iranians are crossing red lines," Israel Minister of Intelligence Yisrael Katz said. "They are playing with fire."